title: Gradual and immediate nicotine reduction result in similar low-dose nicotine self-administration.
abstract: BACKGROUND
  Food and Drug Administration-mandated product standards that drastically reduce nicotine content in cigarettes aim to decrease smoking and thus improve health outcomes for millions of U.S. smokers. Researchers have suggested that nicotine reduction should be implemented gradually, but a gradual nicotine reduction may shift the minimum level of nicotine required to reinforce behavior or may result in different levels of compensatory smoking behavior.
  
  
  METHODS
  Rats were given the opportunity to acquire nicotine self-administration at 60 µg/kg/infusion nicotine with a cocktail of other tobacco constituents included as the vehicle. Rats were subsequently assigned to one of six immediate dose reductions (30, 15, 7.5, 3.75, 1.875, or 0.0 µg/kg/infusion) for 10 sessions (n = 9-15). Rats in the 30 µg/kg/infusion reduction group continued to have their nicotine dose reduced by half after at least 10 sessions at each dose until reaching 1.875 µg/kg/infusion (i.e., gradual reduction).
  
  
  RESULTS
  For both methods of reduction, reduction to 3.75 µg/kg/infusion resulted in significant decreases in behavior. Reduction to doses above 3.75 µg/kg/infusion resulted in only limited compensation. The largest compensation was temporary. There was no compensation following reduction to 3.75 µg/kg/infusion or below.
  
  
  CONCLUSIONS
  This study suggests that reduction to the same nicotine dose will result in similar reductions in behavior for both gradual and immediate reductions, and both methods result in similar compensation. Future studies using humans should investigate differences in other outcomes such as withdrawal and craving.
authors.affiliation: Department of Psychology, School of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA;
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Smith
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Levin
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Schassburger
authors.forename: Deanne M
authors.initials: DM
authors.lastname: Buffalari
authors.forename: Alan F
authors.initials: AF
authors.lastname: Sved
authors.forename: Eric C
authors.initials: EC
authors.lastname: Donny
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D062905:Central Venous Catheters; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D008297:Male; D009538:Nicotine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D000074606:Smoking Prevention; D013997:Time Factors
chemical_list: D009538:Nicotine